CircRNAs在骨关节炎发生发展中的作用

An emerging function of circRNAs in the development and progression of osteoarthritis

环状RNA(circular RNAs,circ RNAs)是一类在真核细胞中广泛存在的非编码RNA。与传统的线性RNA不同,环状RNA无5’末端帽子和3’末端多聚A尾,而是形成一个共价闭合的环状结构。最初,人们认为circ RNAs是前体m RNA(pre-m RNA)发生错误剪接而形成的低丰度RNA分子,没有给予足够重视。随着高通量RNA测序技术和生物信息学的发展,大量circ RNAs被鉴定出来,对其认识也逐渐深入,发现circ RNAs具有重要的生物学功能,在充当mi RNA"海绵"、调控基因转录与表达等方面发挥着重要作用。近几年研究发现,circ RNAs在骨关节炎(osteoarthritis,OA)关节软骨与正常软骨中表达出现差异。部分表达差异的circ RNAs参与调节了与OA发生发展密切相关的软骨细胞外基质(extracellular matrix,ECM)降解、炎症反应、软骨细胞凋亡等过程。尤其是,小干扰RNA(small interfering RNAs,si RNAs)沉默circ RNA-CER后,可促进软骨细胞ECM生成,提示circ RNAs可能成为治疗OA的新靶点。本文将在简单综述circ RNAs的生物合成、主要生物功能的基础上,重点综述circ RNAs与OA发生发展之间的关系,以期为OA的诊断和特异性治疗提供新靶点和新治疗措施。

Circular RNAs（circRNAs） are a novel type of non-coding RNAs（ncRNAs） widely distributed in eukaryotic cells. Unlike canonical linear RNAs, circ RNAs form a covalently closed continuous loop without the 5＇-terminal cap and 3＇-terminal poly A tail. Circ RNAs were originally thought to represent errors in pre-m RNA splicing and did not gain much interest at the time. With the development of high-throughput RNA sequencing technology and bioinformatics, a large number of circ RNAs have been successfully discovered and identified, leading to a resurgence of interest in these molecules. Moreover, evidences are rising that some circ RNAs might regulate mi RNAs serving as mi RNA ‘sponges＇ and play a significant role in regulation of gene transcription and expression. Recently, emerging evidence revealed that circ RNAs are differentially expressed in osteoarthritis（OA） and normal cartilage, and some of which are involved in the pathological process of OA by regulating the chondrocyte extracellular matrix（ECM） degradation, inflammation and apoptosis. Expecially, silencing of circ RNA-CER using small interfering RNA（siRNA） can increase ECM formation, indicating that circRNAs may be new targets for OA treatment. In this review, we briefly delineate the origins and biofunctions of circ RNAs and highlight the association between circ RNAs and OA, providing new targets for OA diagnosis and clinical treatment.